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Related Experiment Videos

Islet cell transplantation tolerance.

A A Rossini1, J P Mordes, D L Greiner

  • 1Department of Medicine, University of Massachusetts Medical School, Worcester 01655, USA. aldo.rossini@umassmed.edu

Transplantation
|March 13, 2002
PubMed
Summary

Inducing immune tolerance for type 1 diabetes islet transplants is crucial. Current methods face challenges with viral infections and memory cells, necessitating strategy modifications for broader clinical application.

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Area of Science:

  • Immunology
  • Transplantation Biology
  • Diabetes Research

Background:

  • Type 1 diabetes (T1D) islet transplantation currently necessitates lifelong immunosuppression.
  • Achieving immune tolerance for islet grafts would eliminate the need for systemic immunosuppression.
  • Previous studies showed costimulatory blockade with donor-specific transfusion and anti-CD154 antibody induces tolerance in mice.

Purpose of the Study:

  • To investigate challenges and potential modifications for translating costimulatory blockade-based tolerance induction into clinical practice for T1D.
  • To address limitations of current tolerance induction protocols, particularly in the context of viral infections and autoimmune models.

Main Methods:

  • Utilized a murine model to assess tolerance induction via costimulatory blockade (donor-specific transfusion + anti-CD154 mAb).

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  • Examined the roles of CD4+ T cells, interferon-gamma, and CTLA4 in the tolerance mechanism.
  • Investigated the impact of viral infection and autoimmune conditions (nonobese diabetic mice) on tolerance induction efficacy.

    • Main Results:

    • Costimulatory blockade achieved permanent islet and prolonged skin allograft survival in mice, dependent on CD4+ T cells, interferon-gamma, and CTLA4.
    • Viral infection during tolerance induction interfered with the process.
    • The tolerance protocol was ineffective in nonobese diabetic mice, suggesting resistance due to memory autoreactive cells.

    Conclusions:

    • Current costimulatory blockade strategies for islet transplantation tolerance face significant hurdles for clinical application.
    • Modifications, potentially involving patient isolation, hematopoietic chimerism, or targeted immune cell/cytokine treatments, are needed.
    • These modifications may enable tolerance induction in T1D patients with pre-existing memory allo- and autoreactive cells.